CN112010752B - Improved preparation method of calcium glucarate - Google Patents
Improved preparation method of calcium glucarate Download PDFInfo
- Publication number
- CN112010752B CN112010752B CN201910466113.3A CN201910466113A CN112010752B CN 112010752 B CN112010752 B CN 112010752B CN 201910466113 A CN201910466113 A CN 201910466113A CN 112010752 B CN112010752 B CN 112010752B
- Authority
- CN
- China
- Prior art keywords
- calcium
- acid
- sodium
- potassium
- glucarate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses an improved preparation method of calcium glucarate, which takes glucose as a raw material, is dissolved, is oxidized by an oxidant in an alkaline environment under the action of a catalyst to obtain glucarate, and is acidified by acid and then generates a target compound with a calcium-containing compound. The method has the advantages of mild reaction conditions, simple operation, less environmental pollution in the whole production process, high yield and suitability for industrial production.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a preparation method of improved calcium glucarate
Background
Calcium glucarate has 4 chiral centers, and is generally present as a 4 hydrate, and has the following structural formula:
glucaric acid is a non-toxic glucose derivative, naturally occurs in fruits such as grapefruit, apple, orange and the like and cruciferous vegetables, and is secreted in a small amount of mammals and human bodies. It also has wide application value in the chemical industry field and the medicine field. For example, the polymer can be used as a basic unit for polymer synthesis to synthesize polyamides, hydroxylated nylons (PHPAs) and polydimethylsiloxane (BDMS) polyamides, to synthesize biodegradable polymers, slow release fertilizers, various films and the like, and can also be used as a raw material to produce nontoxic and biodegradable phosphate substitutes for household detergents, preservatives, concrete admixtures and the like. Glucaric acid can also be used as a chelating agent for metal preservation in electroplating. In 2004, the united states department of energy (DOE) identified glucaric acid as one of the 12 "most valuable biorefinery products" with great economic value.
Calcium glucarate as a derivative of glucaric acid is also beginning to be widely applied to the fields of food and medicine, such as fortified milk powder and dairy products added with D-calcium glucarate, and used as a stabilizer of calcium gluconate injection in the field of medicine, and can also prevent and effectively inhibit esophageal cancer, colon cancer and the like.
CN201910053649.2 discloses a preparation method of calcium glucarate, which comprises the following steps: (1) carrying out catalytic oxidation reaction on glucose, oxygen and a metal catalyst palladium ammonium vanadate in a high-pressure reactor to obtain glucaric acid; (2) adding alkali containing potassium after oxidation reaction, and converting the glucaric acid into glucaric acid potassium salt; (3) reacting potassium glucarate with acid to free glucaric acid; (4) reacting glucaric acid with calcium-containing alkali to obtain calcium glucarate. The preparation method needs to perform oxidation reaction with oxygen under the condition of high pressure, the reaction temperature is 75-120 ℃, and the pressure is 30-50 MPa. The use of the metal catalyst palladium vanadium ammonium has high cost, is not environment-friendly and is not suitable for production amplification. The yield of the calcium glucarate prepared by the method is about 65 percent.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide an improved preparation method of calcium glucarate according to a synthesis concept of green chemistry, and the preparation method has the advantages of mild reaction conditions, simple operation, less environmental pollution in the whole production process, high yield and suitability for industrial production.
In order to achieve the purpose, the main technical scheme provided by the invention is as follows:
an improved preparation method of calcium glucarate comprises the following steps:
(1) glucose is used as a raw material, and is oxidized by an oxidant under the action of a catalyst under the alkaline condition after being dissolved to obtain glucarate;
(2) after acidification, the glucarate reacts with calcium-containing compound to obtain calcium glucarate.
The reaction temperature of the method is-20-80 ℃, and preferably 0-20 ℃.
The solvent used for dissolving is selected from common solvents such as methanol, ethanol, tetrahydrofuran, toluene, water, thionyl chloride, N-dimethylformamide, dimethyl sulfoxide and the like.
The catalyst used in the invention is selected from one or more of common oxidation catalysts such as 5, 5-dimethyl-1-pyrroline-N-oxide, tetramethylpiperidine oxynitride, 5- (diethoxyphosphoryl) -5-methyl-1-pyrroline-N-oxide, sodium bromide, potassium bromide and the like.
The pH value under the alkaline condition is 8-13.
The alkali used for maintaining the alkaline condition is selected from one or more of inorganic or organic alkali such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, pyridine, ethylenediamine and the like.
The oxidant used in the step (1) of the invention is one or more selected from potassium hypochlorite, hydrogen peroxide, peroxyacetic acid, sodium dichromate, chromic acid, nitric acid, potassium permanganate, ammonium persulfate, sodium hypochlorite, sodium percarbonate, sodium perborate, potassium perborate, bromine and iodine.
The acid used for acidification in the step (2) of the invention is one or more selected from inorganic or organic acids such as hydrochloric acid, nitric acid, hydrobromic acid, acetic acid, sulfuric acid, perchloric acid and the like.
The calcium-containing compound used in step (2) of the present invention is one or more selected from inorganic or organic calcium salts such as calcium carbonate, calcium chloride, calcium oxide, calcium bromide, calcium phosphate, calcium citrate, etc.
The invention further comprises a step (3) of pulping the product obtained in the step (2), wherein the pulping solvent is one or more selected from methanol, ethanol, toluene, acetonitrile, water, thionyl chloride and N, N-dimethylformamide.
Compared with the prior art, the invention has the following advantages and effects: 1) avoids the use of noble metal catalyst, and all the raw materials are cheap and easy to obtain, and the production cost is low. 2) The whole production process has less harm to the environment. 3) The experiment can be completed at room temperature within a wider reaction temperature range, high-temperature and high-pressure conditions are not needed, the requirement on equipment is low, and the production safety risk is small. 4) Simple operation, high yield up to 78-83%, and suitability for industrial production.
Detailed Description
The present invention is further illustrated by the following examples, which are illustrative of the present invention and are not to be construed as being limited thereto.
With reference to the method disclosed in CN201910053649.2, the preparation of calcium glucarate was carried out:
the method comprises the following steps:
9g of glucose, 10 mol% of nitric acid (the total amount of the glucose and the oxygen participating in the reaction is 100%), 0.9g of palladium-vanadium-ammonium metal catalyst and 90mL of water are added into a high-pressure reaction tank, the pressure is increased to 40MPa, the temperature is increased to 100 ℃, and the reaction is carried out for 15 hours. After the reaction, the temperature is reduced to room temperature, solid KOH is added into the reaction liquid, and the pH value is adjusted to 9. Cooling the mixture to 0 ℃, adjusting the pH value to 3-4 by using 65% concentrated nitric acid, stirring for 1h, carrying out suction filtration, washing a filter cake for three times by using water, and drying. Pouring 10.2g of dried potassium glucarate into 50ml of pure water, cooling to 0 ℃, adjusting the pH to 1-2 by using 65% concentrated nitric acid, then adding solid CaO to adjust the pH to 6, stirring overnight, performing suction filtration, pulping a filter cake at 50 ℃ for 2h by using pure water, cooling to room temperature, stirring for 30min, performing suction filtration, leaching the filter cake for three times by using pure water, and drying to obtain 9.8g of white solid, wherein the calcium content is 99.7%, and the yield is 67.3%.
The method 2 comprises the following steps:
45g of glucose, 10 mol% of nitric acid (the total amount of the glucose and the oxygen participating in the reaction is 100%), 4.5g of palladium-vanadium-ammonium metal catalyst and 500mL of water are added into a high-pressure reaction tank, the pressure is increased to 40MPa, the temperature is increased to 100 ℃, and the reaction is carried out for 15 hours. After the reaction, the temperature is reduced to room temperature, solid KOH is added into the reaction liquid, and the pH value is adjusted to 9. Cooling the mixture to 0 ℃, adjusting the pH value to 3-4 by using 65% concentrated nitric acid, stirring for 1h, carrying out suction filtration, washing a filter cake for three times by using water, and drying. Pouring 50g of dried glucaric acid potassium salt into 50ml of pure water, cooling to 0 ℃, adjusting the pH to 1-2 by using 65% concentrated nitric acid, then adding solid CaO to adjust the pH to 6, stirring overnight, performing suction filtration, pulping a filter cake at 50 ℃ for 2h by using pure water, cooling to room temperature, stirring for 30min, performing suction filtration, leaching the filter cake for three times by using pure water, and drying to obtain 48.2g of white solid, wherein the calcium content is 100.3%, and the yield is 66.2%.
Example 1 preparation of calcium glucarate:
adding 8kg of tetrahydrofuran into a 20L reaction kettle, stirring, adding 1kg (5.04mol) of dextrose monohydrate, 0.57g (5mmol) of 5, 5-dimethyl-1-pyrroline-N-oxide and 41.2g (0.4mol) of sodium bromide, after the solid is completely dissolved, beginning to dropwise add 3.54kg (10mol) of sodium hypochlorite, controlling the pH value of 8-13 with triethylamine, continuing to stir for reaction for 1h after the dropwise addition is finished, adjusting the pH value to 1-2 with hydrochloric acid aqueous solution, adding 2.79kg (9mol) of calcium phosphate, adjusting the pH value to be neutral with sodium hydroxide aqueous solution after the solid is completely dissolved, stirring for more than 20h at room temperature, filtering, pulping the filter cake for 3 times with methanol, drying the filter cake in an air-blast drying oven at 30-80 ℃ for 36-48 h to obtain 1.26kg of white solid, wherein the calcium content is 99.9%, and the yield is 78.0%.
Example 2 preparation of calcium glucarate:
adding 4.5kg of purified water into a 10L reaction kettle, stirring, adding 450.0g (2.27mol) of dextrose monohydrate, 0.35g (2.27mmol) of tetramethylpiperidine oxynitride and 23.4g (0.227mol) of sodium bromide, after the solid is completely dissolved, beginning to dropwise add 2.41kg (6.81mol) of sodium hypochlorite, controlling the pH value to 8-13 by using sodium hydroxide aqueous solution, continuing to stir for 1h after the dropwise addition is finished, adjusting the pH value to 1-2 by using hydrochloric acid aqueous solution, adding 254.7g (4.54mol) of calcium oxide, stirring for more than 10h at room temperature, filtering, pulping the filter cake by using purified water for 3 times, and drying the filter cake in a forced air drying oven at 30-80 ℃ for 36-48 h to obtain 600.2g of white solid with the calcium content of 100.3% and the yield of 82.5%.
Example 3 preparation of calcium glucarate:
adding 4kg of ethanol into a 10L reaction kettle, stirring, adding 450.0g (2.27mol) of dextrose monohydrate, 0.35g (2.27mmol) of tetramethylpiperidine oxynitride and 27.0g (0.227mol) of potassium bromide, after the solids are completely dissolved, adding 1.60kg (7mol) of ammonium persulfate, controlling the pH value to 8-13 with sodium hydroxide aqueous solution, continuing stirring and reacting for 1h after the dropwise addition is finished, adjusting the pH value to be neutral with hydrochloric acid aqueous solution, adding 566.1g (5.1mol) of calcium chloride, stirring for more than 10h at room temperature, filtering, pulping the filter cake with ethanol for 3 times, drying the filter cake in an air-blast drying oven at 30-80 ℃ for 36-48 h to obtain 587.5g of white solids, wherein the calcium content is 100.8%, and the yield is 80.8%.
Example 4 preparation of calcium glucarate:
adding 4kg of dimethyl sulfoxide into a 10L reaction kettle, stirring, adding 1kg (5.04mol) of dextrose monohydrate, 0.59g (2.5mmol) of 5- (diethoxyphosphoryl) -5-methyl-1-pyrroline-N-oxide and 27.0g (0.227mol) of potassium bromide, after the solid is completely dissolved, adding 1.60kg (7mol) of ammonium persulfate, controlling the pH value of 8-13 by using sodium carbonate aqueous solution, continuously stirring for reaction for 1h after the dropwise addition is finished, adjusting the pH value to be neutral by using hydrochloric acid aqueous solution, adding 566.1g (5.1mol) of calcium chloride, stirring for more than 10h at room temperature, filtering, pulping the filter cake for 3 times by using acetonitrile, drying the filter cake in a blast drying oven at the temperature of 30-80 ℃ for 36-48 h to obtain 1.34kg of white solid, wherein the calcium content is 99.9%, and the yield is 83.0%.
Example 5 preparation of calcium glucarate:
adding 10kg of purified water into a 20L reaction kettle, stirring, adding 1kg (5.04mol) of dextrose monohydrate, 0.59g (2.5mmol) of 5- (diethoxyphosphoryl) -5-methyl-1-pyrroline-N-oxide and 23.4g (0.227mol) of sodium bromide, after the solid is completely dissolved, dropwise adding 1.71kg (15.12mol) of 30% aqueous hydrogen peroxide, controlling the pH value with aqueous sodium carbonate to 8-13, continuously stirring and reacting for 1h after the dropwise adding is finished, adjusting the pH value to 1-2 with aqueous hydrochloric acid, adding 756.7g (7.56mol) of calcium carbonate, after the calcium carbonate is completely dissolved, adjusting the pH value to be neutral with aqueous sodium hydroxide, stirring for more than 10h at room temperature, filtering, pulping the filter cake with water for 3 times, drying the filter cake in an air blast drying oven at 30-80 ℃ for 36-48 h to obtain 1.22kg of white solid, wherein the calcium content is 100.1%, and the yield is 75.6%.
1H-NMR(500MHz,D2O)δ4.44(d,J＝2.9Hz,1H),4.32(d,J＝5.0Hz,1H),4.11(dd,J＝5.4, 3.0Hz,1H),3.94(t,J＝5.2Hz,1H)
13C-NMR(500MHz,D2O)δ＝70.65，70.72，71.00，72.44，174.91，175.25ppm
MS(ESI)：m/z＝104.0112[M-Ca2+]2-/2
Elemental analysis and detection results: the mass percentage of the element C, H is respectively 22.50 percent and 5.04 percent
It should be noted that the above-mentioned embodiments are merely illustrative of the technical concepts and features of the present invention, and are intended to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (7)
1. An improved preparation method of calcium glucarate is characterized by comprising the following steps:
(1) glucose is used as a raw material, after dissolution, glucose is oxidized by an oxidant under the action of a catalyst under the alkaline condition to obtain a glucose diacid salt, the used catalyst is selected from one or more of 5, 5-dimethyl-1-pyrroline-N-oxide, tetramethylpiperidine oxynitride, 5- (diethoxyphosphoryl) -5-methyl-1-pyrroline-N-oxide, sodium bromide and potassium bromide, and the used oxidant is selected from one or more of potassium hypochlorite, hydrogen peroxide, peroxyacetic acid, sodium dichromate, chromic acid, nitric acid, potassium permanganate, ammonium persulfate, sodium hypochlorite, sodium percarbonate, sodium perborate, potassium perborate, bromine and iodine;
(2) acidifying the glucose diacid salt with acid, and reacting with a calcium-containing compound to obtain the glucose diacid calcium, wherein the calcium-containing compound is one or more selected from calcium carbonate, calcium chloride, calcium oxide, calcium bromide, calcium phosphate and calcium citrate.
2. The method for preparing calcium glucarate according to claim 1, characterized in that the reaction temperature in the step (1) is-20 to 80 ℃.
3. The method according to claim 1, wherein the solvent used in the dissolving step (1) is one or more selected from methanol, ethanol, tetrahydrofuran, toluene, acetonitrile, water, thionyl chloride, N-dimethylformamide, and dimethylsulfoxide.
4. The method according to claim 1, wherein the alkaline condition in the step (1) has a pH of 8 to 13.
5. The method according to claim 1, wherein the base used in step (1) for maintaining the alkaline condition is selected from one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, pyridine, and ethylenediamine.
6. The method according to claim 1, wherein the acid used in the acidification in step (2) is selected from one or more of hydrochloric acid, nitric acid, hydrobromic acid, acetic acid, sulfuric acid and perchloric acid.
7. The method according to claim 1, further comprising a step (3) of beating the product obtained in the step (2) with a beating solvent selected from one or more of methanol, ethanol, toluene, acetonitrile, water, thionyl chloride, and N, N-dimethylformamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910466113.3A CN112010752B (en) | 2019-05-30 | 2019-05-30 | Improved preparation method of calcium glucarate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910466113.3A CN112010752B (en) | 2019-05-30 | 2019-05-30 | Improved preparation method of calcium glucarate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112010752A CN112010752A (en) | 2020-12-01 |
| CN112010752B true CN112010752B (en) | 2022-06-14 |
Family
ID=73500536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910466113.3A Active CN112010752B (en) | 2019-05-30 | 2019-05-30 | Improved preparation method of calcium glucarate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112010752B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113854480A (en) * | 2021-09-10 | 2021-12-31 | 徐州工程学院 | Preparation method of functional minced fillet product stored at normal temperature |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678695A (en) * | 2019-01-21 | 2019-04-26 | 江苏东南纳米材料有限公司 | A kind of preparation method of antacidin |
-
2019
- 2019-05-30 CN CN201910466113.3A patent/CN112010752B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678695A (en) * | 2019-01-21 | 2019-04-26 | 江苏东南纳米材料有限公司 | A kind of preparation method of antacidin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112010752A (en) | 2020-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101367760B (en) | Synthesis of 2-chlorine apellagrin | |
| CN112010752B (en) | Improved preparation method of calcium glucarate | |
| CN106699774A (en) | Sulbactam sodium preparation method | |
| CN110156985A (en) | A kind of high fluidity random copolymerization semi-aromatic nylon and preparation method thereof | |
| CN115124465B (en) | Preparation method of quinclorac intermediate | |
| CN113461519A (en) | Preparation method of octadecanedioic acid mono-tert-butyl ester-PFP | |
| CN108440409B (en) | Green and efficient preparation method of rebamipide | |
| EP2438012B1 (en) | Process for the preparation of a composition comprising meso-tartaric acid | |
| CN114213368A (en) | Method for preparing furan dicarboxylic acid by oxidizing 5-hydroxymethylfurfural with composite catalyst | |
| CN115724778B (en) | Preparation method of copper methionine chelate | |
| CN112794375A (en) | Preparation method of manganese dioxide modified nickel-cobalt spinel catalyst | |
| MX2007012492A (en) | New method for the preparation of 6-(3-(1-adamantyl)-4- methoxphenyl)-2-naphthoic acid. | |
| US4052415A (en) | Manufacture of lactones of the triphenylmethane series | |
| CN107602408B (en) | Synthesis method of acetamino diethyl malonate | |
| CN112939893B (en) | Synthesis method of 4- (4-aminophenyl) -3-morpholinone | |
| CN111574387A (en) | P-aminomethyl benzoic acid and preparation method thereof | |
| CN106748718B (en) | Preparation process of ketoprofen | |
| CN107188875A (en) | A kind of Preparation Method And Their Intermediate of substituted benzene phthalein compounds | |
| CN112010793A (en) | Synthetic method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid | |
| CN115448890A (en) | Synthesis process of 5-carboxyl benzotriazole | |
| CN117623903A (en) | Preparation method of D-calcium glucarate | |
| CN111153853B (en) | Preparation method of 2-chloronicotinic acid | |
| CN108329278A (en) | A kind of high-efficiency synthesis method of 5- Chloro-Benzotriazoles | |
| CN112439437B (en) | Iridium-containing solution used as catalyst for synthesizing acetic acid, and preparation method and application thereof | |
| CN117384030A (en) | Production method of bio-based succinic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |